Possible involvement of alpha-2A adrenergic receptors in attention deficit hyperactivity disorder: Radioligand binding and polymorphism studies
| Autor: | D. B. Bylund, Jodi Polaha, Shelley D. Smith, Christopher J. Kratochvil, Carol Ellis, J. D. Deupree, D. Bohac |
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| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty Linkage disequilibrium Adolescent Genotype Adrenergic receptor Population Single-nucleotide polymorphism behavioral disciplines and activities Linkage Disequilibrium Radioligand Assay Cellular and Molecular Neuroscience Receptors Adrenergic alpha-2 Internal medicine mental disorders Radioligand Humans Medicine Attention deficit hyperactivity disorder Genetic Predisposition to Disease Child education Receptor Genetics (clinical) Genetic association education.field_of_study Polymorphism Genetic business.industry medicine.disease Psychiatry and Mental health Endocrinology Attention Deficit Disorder with Hyperactivity Female business Protein Binding |
| Zdroj: | American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. :877-884 |
| ISSN: | 1552-485X 1552-4841 |
| Popis: | Neuropharmacological and genetic association studies have implicated norepinephrine and adrenergic receptors in the pathogenesis of ADHD. The purpose of this study was to compare genetic association studies of three polymorphisms of the alpha-2A adrenergic receptor gene (ADRA2A) with radioligand binding studies of the alpha-2A adrenergic receptor protein in platelets from a sample of children without or with ADHD. The pediatric subjects ranged from 6 to 18 years of age. A thorough clinical assessment of each child resulted in one of the following DSM-IV ADHD diagnoses: inattentive, hyperactive/impulsive, combined, or no ADHD. No significant linkage was found between the ADRA2A polymorphisms (MspI, HhaI, and DraI) and any of the phenotypes tested. Association analysis, however, did detect significant linkage disequilibrium for the DraI polymorphism. Association was also evaluated considering the three ADRA2A single nucleotide polymorphisms as haplotypes. The HhaI-DraI and the MspI-HhaI-DraI haplotypes were significantly associated with ADHD. The platelet alpha-2 adrenergic receptor density did not differ between children without or with ADHD. The affinity of the receptor for the radioligand however, differed significantly between those without and with ADHD. In addition, there were some significant correlations between binding parameters and severity of ADHD in this well-characterized clinical population, and significant association was found between these measures of receptor function and MspI and DraI polymorphisms. Thus, both the genetic and the binding studies indicate that the alpha-2 adrenergic receptor may play a role in ADHD. |
| Databáze: | OpenAIRE |
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